Mammalian cerebral cortex and rat primary visual cortex (area 17) specifically, contain both extrinsic and intrinsic neurons. Axons of extrinsic cells terminate within, but also outside area 17. Cells with intrinsic axons, on the other hand, only connect to targets within the area in which they reside; this cell type has frequently been associated with inhibitory actions which are thought to be crucial for normal cortical functions. The aim of the proposed research are to characterize the morphological and chemical types of intrinsic neurons and to assess the role of identified cells in cortical circuitry. To achieve these goals, anatomical tracing and immunocytochemical techniques will be used in combination with a new and powerful retrograde labeling method for visualizing local projection neurons in vitro. These combined approaches will permit intracellulr electro-physiological recordings and dye injections to be performed on identified, intrinsic cortical neurons in tissue slices. In the initial experiments, particular emphasis will be placed on the characterization of several intrinsic cell types which we previously identified in the geniculate input zone in deep layer 6. Two of these types stain for GABAergic markers, although they probably differ in their colocalization for somatostatin and, thus, may permit the distinction of two intrinsic, putative inhibitory systems. Analysis of these two systems will focus on the spatial distribution of their cell bodies, the vertical and horizontal laminar axonal projection patterns, the spatial relationships to afferent and efferent projection systems and their contribution to a GABAergic lattice in upper layers. Lower layer 6 receives thalamic and cortical afferents and, it is possible that at least one of these intrinsic systems provides monosynaptic input. Intracellular recordings from identified cells in deep layer 6 will, be performed, in order to determine the precise relationships. To examine the postsynaptic effects of the different intrinsic pathways originating in deep layer 6, we will record the responses in different cortical layers to stimulation of layer 6. In addition, we will investigate the possibility that GABA acts as neurotransmitter in some of the intrinsic neurons. Two-electrode experiments, combined with intracellular dye injections and immunocytochemistry, will attempt to identify types of inhibitory neurons and to determine how they are integrated into the intrinsic circuitry. These anatomical and immunocytochemical studies should contribute to the understanding of the organization of intrinsic, cortical system(s), where and how they act to process incoming excitatory activity and, therefore, how they provide for neuronal response properties. The physiological experiments should, in addition, permit determination and characterization of the synaptic responses of these inhibitory neurons and their postsynaptic targets.